Active immunotherapy using anti-idiotypic antibodies which mimic tumor- associated antigens has been shown to be effective in animals and patients. Our proposed research is aimed at optimizing the clinical response of malignant melanoma patients to anti-idiotypic immunotherapy currently under development at IDEC. This will be achieved by "idiotype matching" a therapeutic antibody from a panel of anti-idiotypic antibodies with the individual idiotypic repertoire of the patient. We propose to develop an assay quantitatively determines the frequency of idiotype- responsive B and T cells in prospective idiotype therapy patients. SCID mice will be reconstituted with the peripheral blood lymphocytes from melanoma patients. We will then use the splenic focus assay to determine the frequency of lymphocytes responsive to anti-idiotypic monoclonal antibodies. Furthermore, this SCID splenic focus assay will allow us to analyze the patient's T cell repertoire with respect to T helper cell responses. These "idiotype matching" assays will allow the oncologist to make a rational choice of anti-idiotypic antibodies for immunotherapy of malignant melanoma.